As our living environment is changing or becoming complex or with recent changes in our food life, cases of allergic skin disease are rapidly increasing in number. Exemplary allergic skin diseases are atopic dermatitis and contact dermatitis. Various methods are currently employed to treat these allergic skin diseases and they include avoidance of allergens through a better living environment or a dietary therapy and the administration of anti-allergic agents or steroids. As of today, however, no completely effective method has yet been established to treat allergic skin diseases and a therapeutic drug is desired that is safe to use without developing any side effects and which is capable of exhibiting satisfactory therapeutic efficacy.
Dihomo-γ-linolenic acid (8,11,14-eicosatrienoic acid), which is hereinafter abbreviated as DGLA, is an n-6 polyunsaturated fatty acid contained in breast milk, fish oil, seaweeds, meats, etc. and may be synthesized in vivo from linolic acid via γ-linolenic acid. Heretofore, the physiological actions of the orally administered DGLA precursor γ-linolenic acid have been studied to yield numerous reports concerning hypertension, arterial infarction, complications of diabetes mellitus (neuropathy), and rheumatism, and a lot of cases have also been reported concerning diseases such as atopic dermatitis that involve allergic inflammations (for example, Non-Patent Document 1). A possible anti-inflammatory mechanism of orally administered γ-linolenic acid is speculated to start with conversion of γ-linolenic acid to DGLA which in turn is metabolized by cyclooxigenase or 15-lipoxygenase into prostaglandin E1 (PGE1) which competes with prostaglandin E2 or into 15-hydroxyeicosatrienoic acid (15-HETrE) which inhibits 5-lipoxygenase. As for DGLA, partly because of the lack of a process for its mass production, fewer clinical reports have been published than for γ-linolenic acid. Recently, however, a microorganism-based technology for DGLA production was discovered (Patent Document 1) and an atopy-like dermatitis suppressing action (Patent Document 2) and an anti-arterial infarction action have been reported from experiments with animal models. In those experiments, however, the feed was a mixed diet containing a DGLA oil which was administered orally.
Few studies have been reported on the use of γ-linolenic acid or DGLA as agents for external use, and in the single clinical report of the case where a cream using a γ-linolenic acid containing oil was used in patients with atopic dermatitis, some improvement was recognized in a self-appraisal by the patients themselves but no significant difference was recognized in a doctor's appraisal (Non-Patent Document 2.)
Patent Documents 3 and 4 suggest that essential fatty acids including DGLA be used as agents for external use for skin disease but no working examples were given. Patent Document 5 discloses the COX-2 inhibitory action of DGLA and suggests that it is used in inflammatory skin disease.